Comparison of 18F-FDG-PET/MRI and Whole-Body Diffusion-weighted MRI for Treatment Monitoring of pediatric patients with Hodgkin and Non-Hodgkin Lymphoma

Introduction: Early assessment of treatment response is fundamental in pediatric lymphoma patients to avoid ineffective treatments and enable early stratification. Interim ¹⁸F-FDG positron emission tomography (PET) has shown higher accuracy for therapy response assessment than evaluations of changes in tumor size on conventional imaging [1]. However, sensitivity and specificity of interim ¹⁸F-FDG PET scans vary in different histological lymphoma subtypes [2]. Recently, it has been reported that ionizing radiation-free Whole-Body (WB) Diffusion-Weighted (DW)-MRI has similar sensitivity and specificity compared to ¹⁸F-FDG PET/MRI in children with lymphoma [3]. However, WB-DWI and ¹⁸F-FDG PET response assessments have not been compared by tumor type in the pediatric population. Therefore, purpose of our study was to compare tumor therapy response assessments with ¹⁸F-FDG PET and WB DW-MRI in pediatric patients with Hodgkin lymphoma (HL) and non- Hodgkin Lymphoma (NHL).

Methods: In this non-randomized single-center study we retrospectively enrolled 45 children and young adults with HL (n=20), and NHL (n=25). They were 27 males and 18 females; mean age was 13 years ± 5 [standard deviation]. All patients underwent simultaneous WB DW-MRI, and ¹⁸F-FDG PET scans at baseline and at interim; 36 out of 45 patients also had an end of therapy scan. One radiologist and one nuclear medicine physician reviewed all images in consensus and measured minimum tumor apparent diffusion coefficients (ADC_min) and maximum standardized uptake values (SUV_max) of up to six target lesions. They also assessed therapy response according to Lugano criteria and modified criteria for WB DW-MRI based on ADC value. The agreement between WB DW-MRI and ¹⁸F-FDG PET/MRI-based response classifications as well as the agreement between imaging response on interim scans and clinical response at the end of therapy were calculated with Gwet's agreement coefficient (AC).

Results: After induction chemotherapy, 95% (19 of 20) of patients with HL, and 72% (18 of 25) of patients with NHL showed concordant changes in tumor metabolism and proton diffusion. There was a high agreement between treatment response assessments on interim WB DW-MRI and ¹⁸F-FDG PET (Gwet’s AC = 0.94; 95% confidence interval [CI]: 0.82, 1.00) in patients with HL, and lower agreement for patients with NHL (Gwet’s AC = 0.66; 95% CI: 0.43, 0.90). Similarly, at the end of therapy, the agreement between WB DW-MRI and ¹⁸F-FDG PET was 100% in HL (Gwet’s AC = 1) and 95% in NHL (Gwet’s AC = 0.945; 95% CI: 0.83, 1). In patients with HL, both ¹⁸F-FDG PET and WB DW-MRI based interim response assessments demonstrated 100% agreement with clinical response at the end of therapy. However, in patients with NHL, ¹⁸F-FDG PET demonstrated 80% agreement and WB DW-MRI demonstrates 88% agreement with end of therapy response assessments.¹⁸F-FDG PET and WB DW-MRI showed discordant results compared to end of therapy results in 5 and 3 patients, respectively.

Conclusions: In conclusion, interim chemotherapy response of HL can be evaluated with either ¹⁸F-FDG PET or WB-DW-MRI, while patients with NHL may benefit from a combined approach.

References:

• Lebriz U, Jessica D, Michael L, et al. Value of 18F-FDG PET and PET/CT for Evaluation of Pediatric Malignancies. JNM 2015.

• Jerusalem G, Bequin Y, Najjar F, et al. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of lowgrade non-Hodgkin’s lymphoma (NHL). Ann Oncol 2001.

• Theruvath AJ, Siedek F, Muehe AM, et al. Therapy Response Assessment of Pediatric Tumors with Whole-Body Diffusion-weighted MRI and FDG PET/MRI. Radiology. 2020.